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1.
JCI Insight ; 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39361424

RESUMO

Accumulation of extracellular matrix (ECM) proteins in trabecular meshwork (TM), which leads to increased outflow resistance of aqueous humor and consequently high intraocular pressure, is a major cause of primary open-angle glaucoma (POAG). According to our preliminary research, the RapGAP protein superfamily member, signal-induced proliferation-associated 1-like 1 protein (SIPA1L1), which is involved in tissue fibrosis, may have an impact on POAG by influencing ECM metabolism of TM. This study aims to confirm these findings and identify effects and cellular mechanisms of SIPA1L1 on ECM changes and phagocytosis in human TM (HTM) cells. Our results showed that the expression of SIPA1L1 in HTM cells was significantly increased by TGFß2 treatment in Label-free quantitative proteomics. The aqueous humor and TM cells concentration of SIPA1L1 in POAG patients was higher than that of control. In HTM cells, TGFß2 increased expression of SIPA1L1 along with accumulation of ECM, RhoA and p-Cofilin1. The effects of TGFß2 were reduced by si-SIPA1L1. TGFß2 decreased HTM cell phagocytosis by polymerizing cytoskeletal actin filaments, while si-SIPA1L1 increased phagocytosis by disassembling actin filaments. Simultaneously, overexpressing SIPA1L1 alone exhibited comparable effects to that of TGFß2. Our studies demonstrate that SIPA1L1 not only promotes the production of ECM, but also inhibits its removal by reducing phagocytosis. Targeting SIPA1L1 degradation may become a significant therapy for POAG.

2.
Emerg Microbes Infect ; : 2417864, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39404735

RESUMO

It is believed that DNA double-strand breaks induced by Zika virus (ZIKV) infection in pregnant women is a main reason of brain damage (e.g., microcephaly, severe brain malformation and neuropathy) in newborn babies1,2, but its underlying mechanism is poorly understood. In this study, we report that the depletion of ERp57, a member of the protein disulfide isomerase (PDI) family, leads to the limited production of ZIKV in nerve cells. ERp57 knockout not only suppresses viral induced reactive oxygen species (ROS) mediated host DNA damage, but also decreases apoptosis. Strikingly, DNA damage depends on ERp57-bridged complex formation of viral protein NS2B/NS3. LOC14, an ERp57 inhibitor, restricts ZIKV infection and virus-induced DNA damage. Our work reveals an important role of ERp57 in both ZIKV propagation and virus-induced DNA damage, suggesting a potential target against ZIKV infection.

3.
Immun Inflamm Dis ; 12(10): e70027, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39387442

RESUMO

BACKGROUND: Endotoxic shock, particularly prevalent in intensive care units, represents a significant medical challenge. Endotoxin, upon invading the host, triggers intricate interactions with the innate immune system, particularly macrophages. This activation leads to the production of inflammatory mediators such as tumor necrosis factor-alpha, interleukin-6, and interleukin-1-beta, as well as aberrant activation of the nuclear factor-kappa-B and mitogen-activated protein kinase signaling pathways. OBJECTIVE: This review delves into the intricate inflammatory cascades underpinning endotoxic shock, with a particular focus on the pivotal role of macrophages. It aims to elucidate the clinical implications of these processes and offer insights into potential therapeutic strategies. RESULTS: Macrophages, central to immune regulation, manifest in two distinct subsets: M1 (classically activated subtype) macrophages and M2 (alternatively activated subtype) macrophages. The former exhibit an inflammatory phenotype, while the latter adopt an anti-inflammatory role. By modulating the inflammatory response in patients with endotoxic shock, these macrophages play a crucial role in restoring immune balance and facilitating recovery. CONCLUSION: Macrophages undergo dynamic changes within the immune system, orchestrating essential processes for maintaining tissue homeostasis. A deeper comprehension of the mechanisms governing macrophage-mediated inflammation lays the groundwork for an anti-inflammatory, targeted approach to treating endotoxic shock. This understanding can significantly contribute to the development of more effective therapeutic interventions.


Assuntos
Inflamação , Macrófagos , Choque Séptico , Choque Séptico/imunologia , Humanos , Macrófagos/imunologia , Macrófagos/metabolismo , Animais , Inflamação/imunologia , Ativação de Macrófagos/imunologia , Transdução de Sinais/imunologia , Mediadores da Inflamação/metabolismo , Mediadores da Inflamação/imunologia
4.
Poult Sci ; 103(12): 104321, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39361997

RESUMO

The circadian clock is crucial for maintaining lipid metabolism homeostasis in mammals. Despite the economic importance of fat content in poultry, research on the regulatory effects and molecular mechanisms of the circadian clock on avian hepatic lipid metabolism has been limited. In this study, we observed significant diurnal variations (P<0.05) in triglyceride (TG), free fatty acids (FFA), fatty acid synthase (FAS), and total cholesterol (TC) levels in the chicken embryonic liver under 12-h light/12-h dark incubation conditions, with TG, FFA, and TC concentrations showing significant cosine rhythmic oscillations (P<0.05). However, such rhythmic variations were not observed under complete darkness incubation conditions. Using transcriptome sequencing technology, we identified 157 genes significantly upregulated at night and 313 genes significantly upregulated during the 12-h light/12-h dark cycle. These circadian differential genes are involved in processes and pathways such as lipid catabolic process regulation, meiotic cell cycle, circadian rhythm regulation, positive regulation of the MAPK cascade, and glycerolipid metabolism. Weighted gene co-expression network analysis (WGCNA) revealed 3 modules-green, blue, and red-that significantly correlate with FFA, FAS, and TG, respectively. Genes within these modules were enriched in processes and pathways including the cell cycle, light stimulus response, circadian rhythm regulation, phosphorylation, positive regulation of the MAPK cascade, and lipid biosynthesis. Notably, we identified ten hub genes, including protein kinase C delta (PRKCD), polo like kinase 4 (PLK4), clock circadian regulator (CLOCK), steroid 5 alpha-reductase 3 (SRD5A3), BUB1 mitotic checkpoint serine/threonine kinase (BUB1B), shugoshin 1 (SGO1), NDC80 kinetochore complex component (NDC80), NIMA related kinase 2 (NEK2), minichromosome maintenance complex component 4 (MCM4), polo like kinase 1 (PLK1), potentially link circadian regulation with lipid metabolic homeostasis. These findings demonstrate the regulatory role of the circadian clock in chicken liver lipid metabolism homeostasis and provide a theoretical basis and molecular targets for optimizing the circadian clock to reduce excessive fat deposition in chickens, which is significant for the healthy development of the poultry industry.

5.
J Nanobiotechnology ; 22(1): 623, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39402578

RESUMO

Gliomas are one of the most frequent primary brain tumors and pose a serious threat to people's lives and health. Platelets, a crucial component of blood, have been applied as drug delivery carriers for disease diagnosis and treatment. In this study, we designed engineered nanoplatelets for targeted delivery of therapeutic miR-375 and temozolomide (TMZ, a first-line glioma treatment agent) to enhance glioma therapy. Nanoplatelets were prepared through mild ultrasound, TMZ and miR-375 were co-loaded through ultrasound and electrostatic interactions, respectively, to combine chemotherapy with gene therapy against glioma. To improve the blood brain barrier (BBB) crossing efficiency and glioma targeting ability, the nanoplatelets were modified with central nervous system-specific rabies viral glycoprotein peptide (RVG) through thiol-maleimide click reaction. The RVG modified nanoplatelets co-loaded TMZ and miR-375 (NR/TMZ/miR-375) not only inherited the good stability and remarkable biocompatibility of platelets, but also promoted the cellular uptake and penetration of glioma tissues, and effectively induced cell apoptosis to enhance the therapeutic effect of drugs. In vivo studies showed that NR/TMZ/miR-375 significantly increased the circulation time of TMZ, and exhibited superior combined antitumor effects. In summary, this multifunctional 'natural' nanodrug delivery system provides a potent, scalable, and safety approach for platelet-based combined cancer chemotherapy and gene therapy.


Assuntos
Neoplasias Encefálicas , Sistemas de Liberação de Medicamentos , Glioma , MicroRNAs , Temozolomida , Temozolomida/farmacologia , Temozolomida/química , MicroRNAs/genética , Glioma/tratamento farmacológico , Animais , Humanos , Neoplasias Encefálicas/tratamento farmacológico , Linhagem Celular Tumoral , Camundongos , Sistemas de Liberação de Medicamentos/métodos , Camundongos Nus , Barreira Hematoencefálica/metabolismo , Nanopartículas/química , Apoptose/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Portadores de Fármacos/química , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/química , Glicoproteínas , Fragmentos de Peptídeos , Proteínas Virais
6.
J Neuroinflammation ; 21(1): 250, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39367382

RESUMO

BACKGROUND: IL-2 regulates T cell differentiation: low-dose IL-2 induces immunoregulatory Treg differentiation, while high-dose IL-2 acts as a potent activator of cytotoxic T cells and NK cells. Therefore, high-dose IL-2 has been studied for use in cancer immunotherapy. We aimed to utilize low-dose IL-2 to treat inflammatory diseases such as obesity and insulin resistance, which involve low-grade chronic inflammation. MAIN BODY: Systemic administration of low-dose IL-2 increased Treg cells and decreased inflammation in gonadal white adipose tissue (gWAT), leading to improved insulin sensitivity in high-fat diet-fed obese mice. Additionally, central administration of IL-2 significantly enhanced insulin sensitivity through the activation of the sympathetic nervous system. The sympathetic signaling induced by central IL-2 administration not only decreased interferon γ (IFNγ) + Th1 cells and the expression of pro-inflammatory cytokines, including Il-1ß, Il-6, and Il-8, but also increased CD4 + CD25 + FoxP3 + Treg cells and Tgfß expression in the gWAT of obese mice. These phenomena were accompanied by hypothalamic microgliosis and activation of pro-opiomelanocortin neurons. Furthermore, sympathetic denervation in gWAT reversed the enhanced insulin sensitivity and immune cell polarization induced by central IL-2 administration. CONCLUSION: Overall, we demonstrated that IL-2 improves insulin sensitivity through two mechanisms: direct action on CD4 + T cells and via the neuro-immune axis triggered by hypothalamic microgliosis.


Assuntos
Hipotálamo , Resistência à Insulina , Interleucina-2 , Camundongos Endogâmicos C57BL , Obesidade , Sistema Nervoso Simpático , Animais , Camundongos , Resistência à Insulina/fisiologia , Interleucina-2/metabolismo , Obesidade/metabolismo , Hipotálamo/metabolismo , Hipotálamo/efeitos dos fármacos , Sistema Nervoso Simpático/efeitos dos fármacos , Masculino , Dieta Hiperlipídica/efeitos adversos , Camundongos Obesos , Linfócitos T Reguladores/efeitos dos fármacos
7.
Dose Response ; 22(3): 15593258241282574, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39253070

RESUMO

This study aims to elucidate the anti-hypoxia mechanism of sesamoside, an active component of Phlomis younghusbandii Mukerjee, through a network pharmacology approach. Sesamoside has demonstrated potential anti-oxidant and antiglycation activities. The hypoxia-related disease targets were collected from databases like GeneCards and OMIM. Protein-protein interaction (PPI) networks were constructed using the STRING database. GO/KEGG enrichment analysis was performed using the Metascape database to identify biological processes and signaling pathways. Our results indicate that sesamoside interacts with multiple targets related to glucose and lipid metabolism, nucleotide metabolism, and inflammatory, and we find that AKR1B1 (AR) plays a crucial role in sesamoside responses to hypoxia. Molecular docking studies were performed using Autodock software, revealing good binding activity between sesamoside and AR. We then use CCK-8 assay, qPCR, WB, and ELISA analysis to validate the role of sesamoside in regulating AR and participating in anti-hypoxia through cell experiments. The results show that compared with the hypoxia group, sesamoside treatment significantly improves the expression of AR and inflammation cytokines. In summary, this study sheds light on the anti-hypoxia mechanism of sesamoside using a network pharmacology approach, providing a theoretical basis and experimental foundation for its application in the prevention and treatment of hypoxic diseases.

8.
Haematologica ; 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39234866

RESUMO

Patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have a poor prognosis. Loncastuximab tesirine (Lonca), an antibody conjugate targeting CD19, has demonstrated significant clinical benefit in R/R DLBCL in a global phase 2 LOTIS-2 study. In the China bridging pivotal phase 2 OL-ADCT-402-001 study, eligible patients aged ≥18 years with R/R DLBCL who had failed ≥ 2 lines of systemic therapies were enrolled and treated with Lonca every 3 week with 150 µg/kg for 2 cycles; then 75 µg/kg for subsequent cycles (up to 1 year). The primary endpoint was overall response rate (ORR) assessed by independent review committee. Primary analyses for efficacy and safety were performed on the patients who received at least one treatment and had at least 6 months of follow-up following an initial documented response. As of data-cutoff, 64 patients received Lonca (median: 4.0 cycles [range: 1 to 17]). The median number of prior lines of therapies was 3.0 (range: 2 to 12). The ORR was 51.6% (95% CI: 38.7% to 64.2%), and the complete response rate was 23.4%. Hematological events accounted for the majority of the most common (≥15%) Grade ≥3 treatment-emergent adverse events (TEAEs), in which increased gamma glutamyltransferase (25.0%), and hypokalaemia (18.8%) also were reported. Serious TEAEs were reported in 35 of 64 patients with 4 fatal TEAEs. In conclusion, Lonca monotherapy demonstrated clinically meaningful efficacy and was well-tolerated in heavily pretreated Chinese patients with R/R DLBCL, which was consistent with the results of the LOTIS-2 study in Caucasian patients.

9.
Small ; : e2405586, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39235375

RESUMO

Direct laser writing has gained remarkable popularity by offering architectural control of 3D objects at submicron scales. However, it faces limitations when the fabrication of microstructures comprising multiple materials is desired. The generation processes of multi-material microstructures are often very complex, requiring meticulous alignment, as well as a series of step-and-repeat writing and development of the materials. Here, a novel material system based on multilayers of chemically tailored polymers containing anthraquinone crosslinker units is demonstrated. Upon two-photon excitation, the crosslinkers only require nearby aliphatic C,H units as reaction partners to form a crosslinked network. The desired structure can be written into a solid multi-layered material system, wherein the properties of each material can be designed at the molecular level. In this way, C,H insertion crosslinking (CHic) of the polymers within each layer, along with simultaneous reaction at their interfaces, is performed, leading to the one-step fabrication of multi-material microstructures. A multi-material 3D scaffold with a sixfold symmetry is produced to precisely control the adhesion of cells both concerning surface chemistry and topology. The demonstrated material system shows great promise for the fabrication of 3D microstructures with high precision, intricate geometries and customized functionalities.

10.
Waste Manag ; 190: 174-185, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39326066

RESUMO

Hydrochar, the primary product of hydrothermal carbonization (HTC) of wet organic waste, is recognized as a versatile, carbon-abundant material with diverse applications. However, optimizing its performance for specific uses remains challenging. Therefore, this study introduced a co-HTC process involving carbon-rich lignocellulosic materials and ash-rich livestock manure [i.e., Zanthoxylum bungeanum branch residue (ZB) and swine manure (SM), respectively]. The impacts of HTC temperature (i.e., 180 °C, 220 °C, and 240 °C) and mass ratios (i.e., 1:0, 7:3, 5:5, 3:7, and 0:1) on hydrochar properties (e.g., pH, EC, nutrient contents, heavy metal content and availability, chemical stability, etc) and the characteristics of process water were evaluated. Results reveal that co-HTC dramatically improved the quality of hydrochars compared with that derived from a single feedstock. Notably, the ZB:SM ratio had a more substantial impact on total nutrient content, carbon stability, and heavy metal accumulation and mobility. Additionally, the synergistic effects of ZB and SM were greatly dependent on the HTC temperature. By adjusting the feedstock mass ratio and HTC temperature, a highly-functionalized hydrochar can be produced. For example, hydrochars produced at 240 °C with a 7:3 ZB to SM ratio (HC240-7) is optimal for degraded soil amendment, enhancing carbon sequestration and nutrient supplementation. Results from this study could provide valuable insights for improving waste management through HTC and expanding the environmental and agricultural application of hydrochar.

11.
Adv Sci (Weinh) ; : e2402600, 2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39342418

RESUMO

Temozolomide (TMZ) resistance is one of the major reasons for poor prognosis in patients with glioblastoma (GBM). Long noncoding RNAs (lncRNAs) are involved in multiple biological processes, including TMZ resistance. Linc00942 is a potential regulator of TMZ sensitivity in GBM cells is shown previously. However, the underlying mechanism of TMZ resistance induced by Linc00942 is unknown. In this study, the sequence of Linc00942 by rapid amplification of cDNA ends assay in TMZ-resistant GBM cells is identified and confirmed that Linc00942 contributes to self-renewal and TMZ resistance in GBM cells. Chromatin isolation by RNA purification followed by mass spectrometry (ChIRP-MS) and followed by Western blotting (ChIRP-WB) assays shows that Linc00492 interacted with TPI1 and PKM2, subsequently promoting their phosphorylation, dimerization, and nuclear translocation. The interaction of Linc00942 with TPI1 and PKM2 leads to increased acetylation of H3K4 and activation of the STAT3/P300 axis, resulting in the marked transcriptional activation of SOX9. Moreover, the knockdown of SOX9 reversed TMZ resistance induced by Linc00492 both in vitro and in vivo. In summary, Linc00942 strongly promotes SOX9 expression by interacting with TPI1 and PKM2 is found, thereby driving self-renewal and TMZ resistance in GBM cells. These findings suggest potential combined therapeutic strategies to overcome TMZ resistance in patients with GBM.

12.
J Epidemiol Glob Health ; 14(3): 503-512, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39222226

RESUMO

OBJECTIVE: To analyze the spatial autocorrelation and spatiotemporal clustering characteristics of severe fever with thrombocytopenia syndrome(SFTS) in Anhui Province from 2011 to 2023. METHODS: Data of SFTS in Anhui Province from 2011 to 2023 were collected. Spatial autocorrelation analysis was conducted using GeoDa software, while spatiotemporal scanning was performed using SaTScan 10.0.1 software to identify significant spatiotemporal clusters of SFTS. RESULTS: From 2011 to 2023, 5720 SFTS cases were reported in Anhui Province, with an average annual incidence rate of 0.7131/100,000. The incidence of SFTS in Anhui Province reached its peak mainly from April to May, with a small peak in October. The spatial autocorrelation results showed that from 2011 to 2023, there was a spatial positive correlation(P < 0.05) in the incidence of SFTS in all counties and districts of Anhui Province. Local autocorrelation high-high clustering areas are mainly located in the south of the Huaihe River. The spatiotemporal scanning results show three main clusters of SFTS in recent years: the first cluster located in the lower reaches of the Yangtze River, the eastern region of Anhui Province; the second cluster primarily focused on the region of the Dabie Mountain range, while the third cluster primarily focused on the region of the Huang Mountain range. CONCLUSIONS: The incidence of SFTS in Anhui Province in 2011-2023 was spatially clustered.


Assuntos
Febre Grave com Síndrome de Trombocitopenia , Análise Espaço-Temporal , Humanos , China/epidemiologia , Incidência , Febre Grave com Síndrome de Trombocitopenia/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Análise por Conglomerados , Idoso
13.
Cell Metab ; 36(10): 2262-2280.e5, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39293433

RESUMO

Adipose tissue macrophages (ATMs) play important roles in maintaining adipose tissue homeostasis and orchestrating metabolic inflammation. Given the extensive functional heterogeneity and phenotypic plasticity of ATMs, identification of the authentically pathogenic ATM subpopulation under obese setting is thus necessitated. Herein, we performed single-nucleus RNA sequencing (snRNA-seq) and unraveled a unique maladaptive ATM subpopulation defined as ATF4hiPDIA3hiACSL4hiCCL2hi inflammatory and metabolically activated macrophages (iMAMs), in which PDIA3 is required for the maintenance of their migratory and pro-inflammatory properties. Mechanistically, ATF4 serves as a metabolic stress sensor to transcribe PDIA3, which then imposes a redox control on RhoA activity and strengthens the pro-inflammatory and migratory properties of iMAMs through RhoA-YAP signaling. Administration of Pdia3 small interfering RNA (siRNA)-loaded liposomes effectively repressed adipose inflammation and high-fat diet (HFD)-induced obesity. Together, our data support that strategies aimed at targeting iMAMs by suppressing PDIA3 expression or activity could be a viable approach against obesity and metabolic disorders in clinical settings.


Assuntos
Tecido Adiposo , Macrófagos , Obesidade , Isomerases de Dissulfetos de Proteínas , Animais , Masculino , Camundongos , Tecido Adiposo/metabolismo , Dieta Hiperlipídica/efeitos adversos , Inflamação/metabolismo , Inflamação/patologia , Macrófagos/metabolismo , Doenças Metabólicas/metabolismo , Doenças Metabólicas/patologia , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Obesidade/patologia , Isomerases de Dissulfetos de Proteínas/metabolismo
15.
Microorganisms ; 12(9)2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39338588

RESUMO

Lake microbiota play a crucial role in geochemical cycles, influencing both energy flow and material production. However, the distribution patterns of bacterial communities in lake sediments remain largely unclear. In this study, we used 16S rRNA high-throughput sequencing technology to investigate the bacterial structure and diversity in sediments across different locations (six independent lakes) within Lianhuan Lake and analyzed their relationship with environmental factors. Our findings revealed that both the alpha and beta diversity of sediment bacterial communities varied significantly among the six independent lakes. Furthermore, changes between lakes had a significant impact on the relative abundance of bacterial phyla, such as Pseudomonadota and Chloroflexota. The relative abundance of Pseudomonadota was highest in Habuta Lake and lowest in Xihulu Lake, while Chloroflexota abundance was lowest in Habuta Lake and highest in Tiehala Lake. At the genus level, the relative abundance of Luteitalea was highest in Xihulu Lake compared to the other five lakes, whereas the relative abundances of Clostridium, Thiobacillus, and Ilumatobacter were highest in Habuta Lake. Mantel tests and heatmaps revealed that the relative abundance of Pseudomonadota was significantly negatively correlated with pH, while the abundance of Chloroflexota was significantly positively correlated with total phosphorus and total nitrogen in water, and negatively correlated with electrical conductivity. In conclusion, this study significantly enhances our understanding of bacterial communities in the different lakes within the Lianhuan Lake watershed.

16.
Sensors (Basel) ; 24(18)2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39338842

RESUMO

Finger vein (FV) biometrics have garnered considerable attention due to their inherent non-contact nature and high security, exhibiting tremendous potential in identity authentication and beyond. Nevertheless, challenges pertaining to the scarcity of training data and inconsistent image quality continue to impede the effectiveness of finger vein recognition (FVR) systems. To tackle these challenges, we introduce the visual feature-guided diamond convolutional network (dubbed 'VF-DCN'), a uniquely configured multi-scale and multi-orientation convolutional neural network. The VF-DCN showcases three pivotal innovations: Firstly, it meticulously tunes the convolutional kernels through multi-scale Log-Gabor filters. Secondly, it implements a distinctive diamond-shaped convolutional kernel architecture inspired by human visual perception. This design intelligently allocates more orientational filters to medium scales, which inherently carry richer information. In contrast, at extreme scales, the use of orientational filters is minimized to simulate the natural blurring of objects at extreme focal lengths. Thirdly, the network boasts a deliberate three-layer configuration and fully unsupervised training process, prioritizing simplicity and optimal performance. Extensive experiments are conducted on four FV databases, including MMCBNU_6000, FV_USM, HKPU, and ZSC_FV. The experimental results reveal that VF-DCN achieves remarkable improvement with equal error rates (EERs) of 0.17%, 0.19%, 2.11%, and 0.65%, respectively, and Accuracy Rates (ACC) of 100%, 99.97%, 98.92%, and 99.36%, respectively. These results indicate that, compared with some existing FVR approaches, the proposed VF-DCN not only achieves notable recognition accuracy but also shows fewer number of parameters and lower model complexity. Moreover, VF-DCN exhibits superior robustness across diverse FV databases.


Assuntos
Dedos , Redes Neurais de Computação , Humanos , Dedos/fisiologia , Dedos/irrigação sanguínea , Veias/diagnóstico por imagem , Veias/fisiologia , Processamento de Imagem Assistida por Computador/métodos , Algoritmos , Bases de Dados Factuais , Identificação Biométrica/métodos
17.
Nat Nanotechnol ; 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39209994

RESUMO

In patients with glioblastoma (GBM), upregulated midkine (MDK) limits the survival benefits conferred by temozolomide (TMZ). RNA interference (RNAi) and CRISPR-Cas9 gene editing technology are attractive approaches for regulating MDK expression. However, delivering these biologics to GBM tissue is challenging. Here we demonstrate a polymer-locking fusogenic liposome (Plofsome) that can be transported across the blood-brain barrier (BBB) and deliver short interfering RNA or CRISPR-Cas9 ribonucleoprotein complexes into the cytoplasm of GBM cells. Plofsome is designed by integrating a 'lock' into the fusogenic liposome using a traceless reactive oxygen species (ROS)-cleavable linker so that fusion occurs only after crossing the BBB and entering the GBM tissue with high ROS levels. Our results showed that MDK suppression by Plofsomes significantly reduced TMZ resistance and inhibited GBM growth in orthotopic brain tumour models. Importantly, Plofsomes are effective only at tumour sites and not in normal tissues, which improves the safety of combined RNAi and CRISPR-Cas9 therapeutics.

18.
Bioanalysis ; 16(13): 693-704, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39157863

RESUMO

Aim: Branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) were suggested as potential biomarkers in liver disease. This study aimed to develop and validate a simple and rapid LC-MS/MS method to simultaneously measure serum BCAAs and AAAs levels in patients with liver injury, and further establish reference intervals of Chinese healthy adult populations.Patients & methods: Samples were prepared by a one-step protein precipitation and analysis time was 4 min per run.Results: The validation results showed good linearity (r2 >0.9969), satisfactory accuracy (94.44% - 107.75%) and precision (0.10% - 5.90%).Conclusion: This method proved to be suitable for high-throughput routine clinical use and could be a valuable adjunct diagnosis tool for liver injury and other clinical applications.


[Box: see text].


Assuntos
Aminoácidos Aromáticos , Aminoácidos de Cadeia Ramificada , Espectrometria de Massas em Tandem , Humanos , Espectrometria de Massas em Tandem/métodos , Aminoácidos de Cadeia Ramificada/sangue , Aminoácidos Aromáticos/sangue , Cromatografia Líquida/métodos , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Espectrometria de Massa com Cromatografia Líquida
19.
Water Res ; 264: 122212, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39126743

RESUMO

Ultralow pressure filtration system, which integrates the dual functionalities of biofilm degradation and membrane filtration, has gained significant attention in water treatment due to its superior contaminant removal efficiency. However, it is a challenge to mitigate membrane biofouling while maintaining the high activity of biofilm. This study presents a novel ceramic-based ultrafiltration membrane functionalized with tourmaline nanoparticles to address this challenge. The incorporation of tourmaline nanoparticles enables the release of nutrient elements and the generation of an electric field, which enhances the biofilm activity on the membrane surface and simultaneously alleviates intrapore biofouling. The tourmaline-modified ceramic membrane (TCM) demonstrated a significant antifouling effect, with a substantial increase in water flux by 60 %. Additionally, the TCM achieved high removal efficiencies for contaminants (48.78 % in TOC, 22.28 % in UV254, and 24.42 % in TN) after 30 days of continuous operation. The fouling resistance by various constituents in natural water was individually analyzed using model compounds. The TCM with improved electronegativity and hydrophilicity exhibited superior resistance to irreversible fouling through increased electrostatic repulsion and reduced adhesion to foulants. Comprehensive characterizations and analyses, including interfacial interaction energies, redox reaction processes, and biofilm evolutions, demonstrated that the TCM can release nutrient elements to facilitate the development of functional microbial community within the biofilm, and generate reactive oxygen species (ROS) on the membrane surface to the degrade contaminants and mitigate membrane biofouling. The electric field generated by tourmaline nanoparticles can promote electron transfer in the Fe(III)/Fe(II) cycle, ensuring a stable and sustainable generation of ROS and bactericidal negative ions. These synergistic functions enhance contaminant removal and reduce irreversible fouling of the TCM. This study provides fundamental insights into the role of tourmaline-modified surfaces in enhancing membrane filtration performance and fouling resistance, inspiring the development of high-performance, anti-fouling membranes.


Assuntos
Biofilmes , Incrustação Biológica , Membranas Artificiais , Ultrafiltração , Purificação da Água , Purificação da Água/métodos
20.
Redox Biol ; 76: 103295, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39159596

RESUMO

This article has been withdrawn: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). The authors reached out to the Publisher to alert the Publisher to incorrect text published in the article. After investigating the situation, the journal came to the conclusion that the wrong version of the file was sent by the authors to the production team during the proof stage and the misplaced text was not noticed by the authors when they approved the final version. After consulting with the Editor-in-Chief of the journal, the decision was made to withdraw the current version of the article.

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